CETP Drug Interactions 2 — Questions and Answers
Question 1: Oral fluoroquinolone antibiotics should be taken at least 2 hours before or 6 hours after antacids containing aluminum or magnesium because of which interaction mechanism?
- CYP3A4 inhibition by antacids
- Chelation forming insoluble complexes that reduce fluoroquinolone absorption (Correct answer)
- Increased gastric pH accelerating fluoroquinolone degradation
- Competition for renal tubular secretion
Correct answer: Chelation forming insoluble complexes that reduce fluoroquinolone absorption
Polyvalent cations (Al3+, Mg2+, Ca2+, Fe2+) chelate fluoroquinolones in the GI tract, forming insoluble complexes that are poorly absorbed, significantly reducing antibiotic bioavailability.
Question 2: A patient stabilized on lithium therapy is prescribed ibuprofen for arthritis pain. What pharmacokinetic change should the pharmacist anticipate?
- Decreased lithium levels due to increased renal clearance
- Increased lithium levels due to reduced renal clearance (Correct answer)
- No change in lithium levels
- Decreased ibuprofen efficacy due to lithium competition
Correct answer: Increased lithium levels due to reduced renal clearance
NSAIDs inhibit renal prostaglandin synthesis, reducing renal blood flow and decreasing lithium clearance, which raises lithium plasma levels and increases toxicity risk.
Question 3: Co-administration of simvastatin with which medication carries the highest risk of inducing rhabdomyolysis?
- Metformin
- Gemfibrozil (Correct answer)
- Amlodipine
- Lisinopril
Correct answer: Gemfibrozil
Gemfibrozil inhibits OATP1B1 and CYP2C8, significantly reducing simvastatin clearance and increasing muscle exposure, leading to a markedly elevated risk of myopathy and rhabdomyolysis.
Question 4: Digoxin toxicity risk increases significantly when which electrolyte imbalance is caused by a concomitant medication?
- Hypernatremia
- Hyperkalemia
- Hypokalemia (Correct answer)
- Hypermagnesemia
Correct answer: Hypokalemia
Hypokalemia increases the binding of digoxin to Na+/K+-ATPase and enhances its toxic effects; loop and thiazide diuretics can precipitate this interaction by causing potassium wasting.
Question 5: St. John's Wort (Hypericum perforatum) reduces plasma levels of many medications including cyclosporine and HIV protease inhibitors through which primary mechanism?
- Inhibition of CYP3A4 and P-glycoprotein
- Induction of CYP3A4 and P-glycoprotein (Correct answer)
- Direct chelation of drug molecules in the gut
- Increased renal tubular secretion
Correct answer: Induction of CYP3A4 and P-glycoprotein
St. John's Wort is a potent inducer of CYP3A4 and P-glycoprotein, accelerating the metabolism and efflux of many drugs, leading to subtherapeutic concentrations.
Question 6: Tetracycline antibiotics should be taken on an empty stomach and avoided within 2 hours of dairy products because dairy causes which interaction?
- Alteration of gastric pH reducing tetracycline solubility
- Chelation of tetracycline by calcium ions, reducing absorption (Correct answer)
- Induction of gut CYP enzymes by calcium
- Enhanced tetracycline degradation by gut flora fed by dairy
Correct answer: Chelation of tetracycline by calcium ions, reducing absorption
Calcium ions in dairy products chelate tetracyclines to form poorly soluble, non-absorbable complexes in the GI tract, significantly reducing bioavailability.
Question 7: A patient on warfarin is started on amiodarone for atrial fibrillation. The pharmacist should counsel prescribers to expect which change and take which action?
- Decreased INR; increase warfarin dose
- Increased INR; reduce warfarin dose and increase monitoring (Correct answer)
- No change in INR; no adjustment needed
- Decreased INR; discontinue amiodarone
Correct answer: Increased INR; reduce warfarin dose and increase monitoring
Amiodarone inhibits CYP2C9 (and CYP3A4), substantially reducing warfarin clearance and elevating INR; the warfarin dose typically needs to be reduced by 30-50% with close INR monitoring.
CETP Drug Interactions 2
Oral fluoroquinolone antibiotics should be taken at least 2 hours before or 6 hours after antacids containing aluminum or magnesium because of which interaction mechanism?